Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly non-alcoholic fatty liver disease, NAFLD) is a common chronic liver disease strongly linked to obesity, metabolic syndrome (MetS), and type 2 diabetes. It starts as benign hepatic steatosis, but may progress to severe fibrosis, cirrhosis, or hepatocellular carcinoma. Today, MASLD represents one of the leading indications for liver transplantation. This review summarizes current knowledge on MASLD, including its pathogenesis, management strategies, regional disparities, and its specific relevance to women's health. The influence of sex hormones on MASLD has been documented. Polycystic ovary syndrome (PCOS) and the menopause increase MASLD prevalence by more than twofold. Moreover, PCOS increases the risk and severity of MASLD, independent of BMI. The role of menopausal hormone replacement therapy in MASLD remains controversial. However, transdermal estrogen and micronized progesterone or dydrogesterone seem to be more appropriate options. In pregnancy, MASLD is associated with >3-fold increased risk of gestational diabetes and preeclampsia. It may also increase the risk of MASLD development in the offspring-an effect that appears to be mitigated by breastfeeding for longer than six months. Given these findings, it is essential that clinicians involved in women's healthcare are aware of MASLD and its implications across the female lifespan.
Keywords: MASH; MASLD; NAFLD; NASH; gestational diabetes; hormone therapy; menopause; polycystic ovary syndrome; pregnancy; steatosis; steatotic liver disease.
Understanding MASLD: a growing women’s health concernMetabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is one of the most common chronic liver conditions today. It is closely linked to obesity, type 2 diabetes, and MetS. MASLD often begins as a simple fat buildup in the liver (steatosis), but over time, it can lead to serious complications such as liver scarring (fibrosis), cirrhosis, or even liver cancer. In fact, MASLD is now a leading reason for liver transplantation. This disease affects both men and women, but recent research highlights its impact on women’s health. Female sex hormones appear to influence MASLD risk. Conditions like PCOS and menopause significantly increase a woman’s likelihood of developing MASLD. Notably, women with PCOS are at higher risk of developing more severe liver disease, even if they are not overweight. The effect of the use of hormone replacement therapy (HRT) on MASLD is not clear. However, certain forms of HRT, like estrogen patches and progesterone that is chemically identical to the natural one, seem to be safer options for women with this condition who are considering HRT. MASLD can also pose some risks during pregnancy. It increases the risk for gestational diabetes and preeclampsia. Additionally, the presence of MASLD during a pregnancy might increase the child’s own risk of developing liver disease later in life. Fortunately, breastfeeding for more than six months may help reduce this risk. There is fast-growing and promising research in the field of MASLD management with medications. However, the most effective interventions still relate to lifestyle change, exercise and a healthy diet. In conclusion, MASLD has wide-reaching effects throughout a woman’s life, therefore, health providers who care for women should be aware of this condition and how to manage it effectively.